Methods Of Preparing Thiazolidines

Abstract

The present invention provides methods of preparing thiazolidines, and in particular methods of preparing ribose-cysteine.

1 . A method of preparing a thiazolidine comprising:
 a) contacting a sugar and a cysteine with an aqueous solution under suitable conditions to form the thiazolidine;   b) isolating the thiazolidine; and   c) optionally drying the thiazolidine for a sufficient period of time to yield an anhydrous thiazolidine.   
     
     
         2 . The method of  claim 1  wherein the sugar is aldose or ketose monosaccharide, wherein said aldose or ketose monosaccharide is glyceraldehyde, glucose, ribose, or fructose. 
     
     
         3 . The method of  claim 1  wherein the cysteine is free of cystine. 
     
     
         4 . The method of  claim 1  wherein:
 a) the sugar is contacted with the aqueous solution before the cysteine is contacted with the aqueous solution; or 
 b) wherein the cysteine is contacted with the solution after the sugar is completely dissolved. 
 
     
     
         5 . The method of  claim 1  further comprising contacting the solution with an alcohol. 
     
     
         6 . The method of  claim 5  wherein cysteine and an alcohol are contacted with the solution after the sugar is completely dissolved or the cysteine and an alcohol are contacted with the solution simultaneously. 
     
     
         7 . The method of  claim 6  wherein the method comprises in the following order:
 i) contacting the sugar with the aqueous solution to form a sugar solution; 
 ii) contacting the cysteine with the sugar solution of i); and 
 iii) contacting the alcohol with the solution of ii). 
 
     
     
         8 . The method of  claim 1  wherein the isolating comprises precipitating the thiazolidine, wherein the thiazolidine is precipitated by contacting the solution with an alcohol and optionally, wherein the precipitated thiazolidine is washed with a washing agent. 
     
     
         9 . The method of  claim 1  wherein the method yields at least 95% of a calculated theoretical yield and/or the thiazolidine is at least 99% pure as determined by HPLC. 
     
     
         10 . The method of  claim 1  wherein the thiazolidine comprises less than 225 ppm of an alcohol. 
     
     
         11 . The method of  claim 1  wherein the isolated thiazolidine comprises a monohydrate thiazolidine. 
     
     
         12 . The method of  claim 1  wherein the isolated thiazolidine consists of anhydrous thiazolidine. 
     
     
         13 . The method of  claim 1  wherein the thiazolidine is RibCys, GlcCys, GlycCys, FruCys, GlcNH 2 Cys, GlcNHAcCys, and/or any combination thereof. 
     
     
         14 . A method of preparing a thiazolidine comprising:
 a) contacting an aldose or ketose monosaccharide or an amino sugar, and a cysteine with an aqueous solution under conditions to form the thiazolidine;   b) precipitating the thiazolidine; and   c) vacuum drying the thiazolidine at a temperature that is less than or equal to 65° C.,   wherein the aqueous solution optionally comprises ethanol.   
     
     
         15 . The method of  claim 14  wherein the thiazolidine is RibCys, GlcCys, GlycCys, FruCys, GlcNH 2 Cys, GlcNHAcCys, and/or any combination thereof. 
     
     
         16 . A method of preparing a thiazolidine comprising in the following order:
 a) contacting an aldose or ketose monosaccharide or an amino sugar with an aqueous solution;   b) contacting the solution of step a) with a cysteine and ethanol;   c) precipitating the solution of step b) to yield a thiazolidine precipitate; and   d) vacuum drying the thiazolidine precipitate.   
     
     
         17 . The method of  claim 16  wherein step b) comprises in the following order:
 i) contacting the solution of step a) with the cysteine; and 
 ii) contacting the solution of step i) with the ethanol. 
 
     
     
         18 . The method of  claim 16  wherein the thiazolidine is RibCys, GlcCys, GlycCys, FruCys, GlcNH 2 Cys, GlcNHAcCys, and/or any combination thereof.